The long-term objective of these studies remains to identify the metabolic defect in nephropathic cystinosis. We have previously shown that addition of bovine serum albumin to cultures of cystine depleted cystinotic fibroblasts results in a concentration dependent increase in the intralysosomal cystine content. We are now studying proteolysis of a variety of cystine and cysteine containing proteins by cultures of normal and cystinotic fibroblasts to determine if the metabolic defect in cystinotic cells is the result of a deficient cellular or lysosomal disulfide reductase, or a defect in the lysosomal transport of cystine.